By NICHOLAS WADE
March 7, 2006
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Providing the strongest evidence yet that humans are
still evolving, researchers have detected some 700
regions of the human genome where genes appear to have
been reshaped by natural selection, a principal force of
evolution, within the last 5,000 to 15,000 years.

The genes that show this evolutionary change include
some responsible for the senses of taste and smell,
digestion, bone structure, skin color and brain
function.

Many of these instances of selection may reflect the
pressures that came to bear as people abandoned their
hunting and gathering way of life for settlement and
agriculture, a transition well under way in Europe and
East Asia some 5,000 years ago.

Under natural selection, beneficial genes become more
common in a population as their owners have more
progeny.

Three populations were studied, Africans, East Asians
and Europeans. In each, a mostly different set of genes
had been favored by natural selection. The selected
genes, which affect skin color, hair texture and bone
structure, may underlie the present-day differences in
racial appearance.

The study of selected genes may help reconstruct many
crucial events in the human past. It may also help
physical anthropologists explain why people over the
world have such a variety of distinctive appearances,
even though their genes are on the whole similar, said
Dr. Spencer Wells, director of the Genographic Project
of the National Geographic Society.

The finding adds substantially to the evidence that
human evolution did not grind to a halt in the distant
past, as is tacitly assumed by many social scientists.
Even evolutionary psychologists, who interpret human
behavior in terms of what the brain evolved to do, hold
that the work of natural selection in shaping the human
mind was completed in the pre-agricultural past, more
than 10,000 years ago.

"There is ample evidence that selection has been a major
driving point in our evolution during the last 10,000
years, and there is no reason to suppose that it has
stopped," said Jonathan Pritchard, a population
geneticist at the University of Chicago who headed the
study.

Dr. Pritchard and his colleagues, Benjamin Voight,
Sridhar Kudaravalli and Xiaoquan Wen, report their
findings in today’s issue of PLOS-Biology.

Their data is based on DNA changes in three populations
gathered by the HapMap project, which built on the
decoding of the human genome in 2003. The data, though
collected to help identify variant genes that contribute
to disease, also give evidence of evolutionary change.

The fingerprints of natural selection in DNA are hard to
recognize. Just a handful of recently selected genes
have previously been identified, like those that confer
resistance to malaria or the ability to digest lactose
in adulthood, an adaptation common in Northern Europeans
whose ancestors thrived on cattle milk.

But the authors of the HapMap study released last
October found many other regions where selection seemed
to have occurred, as did an analysis published in
December by Robert K. Moysis of the University of
California, Irvine.

Dr. Pritchard’s scan of the human genome differs from
the previous two because he has developed a statistical
test to identify just genes that have started to spread
through populations in recent millennia and have not yet
become universal, as many advantageous genes eventually
do.

The selected genes he has detected fall into a handful
of functional categories, as might be expected if people
were adapting to specific changes in their environment.
Some are genes involved in digesting particular foods
like the lactose-digesting gene common in Europeans.
Some are genes that mediate taste and smell as well as
detoxify plant poisons, perhaps signaling a shift in
diet from wild foods to domesticated plants and animals.

Dr. Pritchard estimates that the average point at which
the selected genes started to become more common under
the pressure of natural selection is 10,800 years ago in
the African population and 6,600 years ago in the Asian
and European populations.

Dr. Richard G. Klein, a paleoanthropologist at Stanford,
said that it was hard to correlate the specific gene
changes in the three populations with events in the
archaeological record, but that the timing and nature of
the changes in the East Asians and Europeans seemed
compatible with the shift to agriculture. Rice farming
became widespread in China 6,000 to 7,000 years ago, and
agriculture reached Europe from the Near East around the
same time.

Skeletons similar in form to modern Chinese are hard to
find before that period, Dr. Klein said, and there are
few European skeletons older than 10,000 years that look
like modern Europeans.

That suggests that a change in bone structure occurred
in the two populations, perhaps in connection with the
shift to agriculture. Dr. Pritchard’s team found that
several genes associated with embryonic development of
the bones had been under selection in East Asians and
Europeans, and these could be another sign of the
forager-to-farmer transition, Dr. Klein said.

Dr. Wells, of the National Geographic Society, said Dr.
Pritchard’s results were fascinating and would help
anthropologists explain the immense diversity of human
populations even though their genes are generally
similar. The relative handful of selected genes that Dr.
Pritchard’s study has pinpointed may hold the answer, he
said, adding, "Each gene has a story of some pressure we
adapted to."

Dr. Wells is gathering DNA from across the globe to map
in finer detail the genetic variation brought to light
by the HapMap project.

Dr. Pritchard’s list of selected genes also includes
five that affect skin color. The selected versions of
the genes occur solely in Europeans and are presumably
responsible for pale skin. Anthropologists have
generally assumed that the first modern humans to arrive
in Europe some 45,000 years ago had the dark skin of
their African origins, but soon acquired the paler skin
needed to admit sunlight for vitamin D synthesis.

The finding of five skin genes selected 6,600 years ago
could imply that Europeans acquired their pale skin much
more recently. Or, the selected genes may have been a
reinforcement of a process established earlier, Dr.
Pritchard said.

The five genes show no sign of selective pressure in
East Asians.

Because Chinese and Japanese are also pale, Dr.
Pritchard said, evolution must have accomplished the
same goal in those populations by working through
different genes or by changing the same genes – but many
thousands of years before, so that the signal of
selection is no longer visible to the new test.

Dr. Pritchard also detected selection at work in brain
genes, including a group known as microcephaly genes
because, when disrupted, they cause people to be born
with unusually small brains.

Dr. Bruce Lahn, also of the University of Chicago,
theorizes that successive changes in the microcephaly
genes may have enabled the brain to enlarge in primate
evolution, a process that may have continued in the
recent human past.

Last September, Dr. Lahn reported that one microcephaly
gene had recently changed in Europeans and another in
Europeans and Asians. He predicted that other brain
genes would be found to have changed in other
populations.

Dr. Pritchard’s test did not detect a signal of
selection in Dr. Lahn’s two genes, but that may just
reflect limitations of the test, he and Dr. Lahn said.
Dr. Pritchard found one microcephaly gene that had been
selected for in Africans and another in Europeans and
East Asians. Another brain gene, SNTG1, was under heavy
selection in all three populations.

"It seems like a really interesting gene, given our
results, but there doesn’t seem to be that much known
about exactly what it’s doing to the brain," Dr.
Pritchard said.

Dr. Wells said that it was not surprising the brain had
continued to evolve along with other types of genes, but
that nothing could be inferred about the nature of the
selective pressure until the function of the selected
genes was understood.

The four populations analyzed in the HapMap project are
the Yoruba of Nigeria, Han Chinese from Beijing,
Japanese from Tokyo and a French collection of Utah
families of European descent. The populations are
assumed to be typical of sub-Saharan Africa, East Asia
and Europe, but the representation, though presumably
good enough for medical studies, may not be exact.

Dr. Pritchard’s test for selection rests on the fact
that an advantageous mutation is inherited along with
its gene and a large block of DNA in which the gene
sits. If the improved gene spreads quickly, the DNA
region that includes it will become less diverse across
a population because so many people now carry the same
sequence of DNA units at that location.

Dr. Pritchard’s test measures the difference in DNA
diversity between those who carry a new gene and those
who do not, and a significantly lesser diversity is
taken as a sign of selection. The difference disappears
when the improved gene has swept through the entire
population, as eventually happens, so the test picks up
only new gene variants on their way to becoming
universal.